‘Scientific rigor and the art of motorcycle maintenance‘ was another recent fine analysis on reliability issues in current biomedicine (Munafo et al. Nat Biotechnol. 32:871-3). If you only want to read one article, this may be it. It nicely sums up the problems and suggests all the relevant measures (see most of my previous posts). But besides the reference to Robert Pirsig’s 1974 novel, what is new on the article is the comparison of the scientific enterprise to the automobile industry, which successfully responded to quality problems with structured quality control (for a more thorough treatment, see the previous post on trust and auditing). Here is their conclusion:
‘Science is conducted on the principle that it is self-correcting, but the extent to which this is true is an empirical question. The more that quality control becomes integrated into the scientific process itself, the more the whole process becomes one of continual improvement. Implementing this at the level of production implies a culture of incentivizing, educating and empowering those responsible for production, rather than policing quality after the fact with ‘quality inspectors’ (i.e., peer reviewers) or, even more distally, requiring attempts at replication. We think this insight, applied successfully to automobile manufacturing in the 1970s, can also be profitably applied to the practice of scientific research to build a more solid foundation of knowledge and accelerate the research endeavor.’
It is time to act!
Many of the concrete measures proposed to improve the quality and robustness of biomedical research are greeted with great skepticism: ‘Good idea, but how can we implement it, and will it work?’. So here are a few recent best practice examples regarding two key areas: Replication, and the review process. Continue reading
Since the 17th century, when gentlemen scientists were typically seen as trustworthy sources for the truth about humankind and the natural order the tenet is generally accepted that ‘science is based on trust‘. This refers to trust between scientists, as they build on each others data and may question a hypothesis, or a conclusion, but not the quality of the scientifc method applied or the faithfulness of the report, such as a publication. But it also refers to the trust of the public in the scientists which societies support via tax-funded academic systems. Consistently, scientists (in particular in biomedicine) score highest among all professions in ‘trustworthiness’ ratings. Despite often questioning the trustworthiness of their competitors when chatting over a beer or two, they publically vehemently argue against any measure proposed to underpin confidence in their work by any form of scrutiny (e.g. auditing). They instead swiftly invoke Orwellian visions of a ‘science police’ and point out that scrutiny would undermine trust and jeopardize the creativity and ingenuity inherent to the scientific process. I find this quite remarkable. Why should science be exempt from scrutiny and control, when other areas of public and private life sport numerous checks and balances? Science may indeed be the only domain in society which is funded by the public and gets away with strictly rejecting accountability. So why do we trust scientists, but not bankers?
Amidst what has been termed ‘reproducibility crisis’ (see also a number of previous posts) in June 2014 the National Institutes of Health and Nature Publishing Group had convened a workshop on the rigour and reproducibility of preclinical biomedicine. As a result, last week the NIH published ‘Principles and Guidelines for Reporting Preclinical Research‘, and Nature as well as Science ran editorials on it. More than 30 journals, including the Journal of Cerebral Blood Flow and Metabolism, are endorsing the guidelines. The guidelines cover rigour in statistical analysis, transparent reporting and standards (including randomization and blinding as well as sample size justification), and data mining and sharing. This is an important step forward, but implementation has to be enforced and monitored: The ARRIVE guidelines (many items of which reappear in the NIH guidelines) have not been adapted widely yet (see previous post). In this context I highly recommend the article by Henderson et al in Plos Medicine in which they systematically review existing guidelines for in vivo animal experiments. From this the STREAM collaboration distilled a checklist on internal, external, and construct validity which I found more comprehensive and relevant than the one published now by the NIH. In the end, however, it is not so relevant to which guideline (ARRIVE, NIH, STREAM, etc.) researchers, reviewers, editors, or funders comply, but rather whether they use one at all!
Note added 12/15/2014: Check out the PubPeer postpublication discussion on the NIH/Nature/Science initiative (click here)!
I have earlier posted on the many virtues of post-publication commenting. Only few journals presently allow readers to comment, discuss, or criticise papers online. Since 2013 the National Library of Medicine of the US National Institutes of Health, which provides us with more than 24 million citations of the MEDLINE, offers a tool to comment on any of these millions of articles: PubMed COMMONS. Although it had a slow start, and at present only less than 3000 comments are listed, it is almost doomed to be a success and has the potential to propel biomedical publishing into the 21st century. I believe that the PubMed COMMONS model is superior to post-publication commenting schemes of indvidual journals. The main advantage of their model is that every article which receives a comment is directly visible and accessible with one click for everyone retrieving the article via PubMed. Comments published in individual journals may be burried on their websites, only a tiny fraction of journals allow commenting, and no other model would allow commenting on papers dating back more than a few years. How does it work?
In 2005 PLOS Medicine published John Ioannidis’ paper ‘Why most published research findings are false’ . The article was a wake up call for many, and now is probably the most influential publication in biomedicine of the last decade (>1.14 Mio views on the PLOS Med webside, thousands of citations in the scientific and lay press, featured in numerous blog posts, etc.). Its title has never been refuted, if anything, it has been replicated, for examples see some of the posts of this blog. Almost 10 years after, Ioannidis now revisits his paper, and the more constructive title ‘How to make more published research true” (PLoS Med. 2014 Oct 21;11(10):e1001747. doi: 10.1371/journal.pmed.1001747.) already indicates that the thrust this time is more forward looking. The article contains numerous suggestions to improve the research enterprise, some subtle and evolutionary, some disruptive and revolutionary, but all of them make a lot of sense. A must read for scientists, funders, journal editors, university administrators, professionals in the health industry, in other words: all stakeholders within the system!
Riddle me this:
What does it mean if a result is reported as significant at p < 0.05?
A If we were to repeat the analysis many times, using new data each time, and if the null hypothesis were really true, then on only 5% of those occasions would we (falsely) reject it.
B Without knowing the statistical power of the experiment, and not knowing the prior probability of the hypothesis, I cannot estimate the probability whether a significant research finding (p < 0.05) reflects a true effect.
C The probability that the result is a fluke (the hypothesis was wrong, the drug doesn’t work, etc.), is below 5 %. In other words, there is a less than 5 % chance that my results are due to chance.
(solution at the end of this post)
Be honest, although it doesn’t sound very sophisticated (as opposed to A and B), you were tempted to chose C, since it makes a lot of sense, and represents your own interpretation of the p-value when reading and writing papers. You are in good company. But is C really the correct answer?